Identification and isolation of a membrane protein necessary for leukotriene production.
Several inflammatory diseases, including asthma, arthritis and psoriasis are associated with the production of leukotrienes by neutrophils, mast cells and macrophages. The initial enzymatic step in the formation of leukotrienes is the oxidation of arachidonic acid by 5-lipoxygenase (5-LO) to leukotriene A4. Osteosarcoma cells transfected with 5-LO express active enzyme in broken cell preparations, but no leukotriene metabolites are produced by these cells when stimulated with the calcium ionophore A23187, indicating that an additional component is necessary for cellular 5-LO activity. A new class of indole leukotriene inhibitor has been described that inhibits the formation of cellular leukotrienes but has no direct inhibitory effect on soluble 5-LO activity. We have now used these potent agents to identify and isolate a novel membrane protein of relative molecular mass 18,000 which is necessary for cellular leukotriene synthesis.
Miller
D K
DK
Department of Biochemistry and Molecular Biology, Merck Institute for Therapeutic Research, Rahway, New Jersey 07065.
Gillard
J W
JW
Vickers
P J
PJ
Sadowski
S
S
Léveillé
C
C
Mancini
J A
JA
Charleson
P
P
Dixon
R A
RA
Ford-Hutchinson
A W
AW
Fortin
R
R
D000345:Affinity Labels / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001386:Azides / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology*; D007249:Inflammation; D007700:Kinetics; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000097:blood* / Q000302:isolation & purification; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009504:Neutrophils / Q000378:metabolism*; D051381:Rats; D002722:Chlorobenzenes
D000345:Affinity Labels; D001386:Azides; D007211:Indoles; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D008565:Membrane Proteins; C060893:MK-886; D002722:Chlorobenzenes; C062610:L 669083